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OBJECTIVE: Accurate prediction of survival prognosis is helpful to guide clinical decision-making. The aim of this study was to develop a model using machine learning techniques to predict the occurrence of composite thromboembolic events (CTEs) in elderly patients with atrial fibrillation(AF). These events encompass newly diagnosed cerebral ischemia events, cardiovascular events, pulmonary embolism, and lower extremity arterial embolism. METHODS: This retrospective study included 6,079 elderly hospitalized patients (≥ 75 years old) with AF admitted to the People's Liberation Army General Hospital in China from January 2010 to June 2022. Random forest imputation was used for handling missing data. In the descriptive statistics section, patients were divided into two groups based on the occurrence of CTEs, and differences between the two groups were analyzed using chi-square tests for categorical variables and rank-sum tests for continuous variables. In the machine learning section, the patients were randomly divided into a training dataset (n = 4,225) and a validation dataset (n = 1,824) in a 7:3 ratio. Four machine learning models (logistic regression, decision tree, random forest, XGBoost) were trained on the training dataset and validated on the validation dataset. RESULTS: The incidence of composite thromboembolic events was 19.53%. The Least Absolute Shrinkage and Selection Operator (LASSO) method, using 5-fold cross-validation, was applied to the training dataset and identified a total of 18 features that exhibited a significant association with the occurrence of CTEs. The random forest model outperformed other models in terms of area under the curve (ACC: 0.9144, SEN: 0.7725, SPE: 0.9489, AUC: 0.927, 95% CI: 0.9105-0.9443). The random forest model also showed good clinical validity based on the clinical decision curve. The Shapley Additive exPlanations (SHAP) showed that the top five features associated with the model were history of ischemic stroke, high triglyceride (TG), high total cholesterol (TC), high plasma D-dimer, age. CONCLUSIONS: This study proposes an accurate model to stratify patients with a high risk of CTEs. The random forest model has good performance. History of ischemic stroke, age, high TG, high TC and high plasma D-Dimer may be correlated with CTEs.
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Fibrilação Atrial , Técnicas de Apoio para a Decisão , Aprendizado de Máquina , Valor Preditivo dos Testes , Tromboembolia , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Feminino , Masculino , Idoso , Estudos Retrospectivos , Medição de Risco , China/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Fatores de Risco , Idoso de 80 Anos ou mais , Incidência , Prognóstico , Fatores Etários , Reprodutibilidade dos Testes , População do Leste AsiáticoRESUMO
BACKGROUND: Poplar in China has long been plagued by the fall webworm Hyphantria cunea. Enhancing plant immunity using chemical elicitors is an environmentally friendly approach to pest control. The phytohormone methyl jasmonate (MeJA) can stimulate the chemical defenses of poplars against herbivores but has been shown to have limited efficacy in practice. Here, we studied the effects of a MeJA and mesoporous silica nanoparticle (MSN) complex (MeJA@MSN) regarding the induction of poplar resistance to H. cunea, which may provide strategies for the effective use of MeJA. RESULTS: The silicon-based phytohormone complex (MeJA@MSNs) exhibited excellent biological and physiochemical properties, such as excellent biocompatibility and plant tissue transportability. The changes in metabolites in poplar leaves induced by MeJA, MSNs, and MeJA@MSNs were investigated by metabolic analysis. MeJA@MSNs led to highly potent induced resistance along with elevated salicylaldehyde content, which increased with the dose administered. The salicylaldehyde metabolite showed a strong antifeedant effect on H. cunea larvae at a dosage of 1 µg, with the 50% lethal dose being 20.4 µg/mg. Furthermore, transcriptional analysis showed that MeJA@MSNs upregulated key genes in biosynthetic pathways more than MeJA and MSNs. CONCLUSION: Our results show that MeJA and MSNs interact positively in poplar, leading to salicylaldehyde accumulation and increased induced resistance to H. cunea, providing new insights into the underlying resistance mechanisms induced by MeJA@MSNs. © 2024 Society of Chemical Industry.
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INTRODUCTION: Serum lipid profiles play a crucial role in diagnosing and evaluating cardiovascular diseases. However, the presence of paraprotein can lead to inaccurate dyslipidemia results on automated analyzers. CASE REPORT: A 65-year-old woman whose combined concentrations of HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) consistently surpassed her total serum cholesterol levels over a period of three months presented with unusual lipid component detection. Further analysis revealed the presence of a monoclonal paraprotein, identified as an IgMλ band, with a concentration of 28.0 g/L. The patient was subsequently diagnosed with Waldenström macroglobulinemia. The use of abnormal reaction kinetic curves and the ß quantification method, along with an alternative method that did not suffer from interference, revealed that the monoclonal paraprotein interfered with the measurements of HDL-C, LDL-C, apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB) when using the Roche detection system. This interference led to spurious elevated HDL-C concentrations and falsely decreased apoA-I and apoB concentrations, while the LDL-C results were minimally affected. Although diluting the sample normalized the HDL-C and LDL-C measurements, the interference with the apoA-I and apoB assays persisted. No other common biochemical tests were interfered with this paraprotein. CONCLUSION: Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable.
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Dislipidemias , Paraproteínas , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/complicações , Idoso , Feminino , Paraproteínas/análise , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/complicações , HDL-Colesterol/sangue , LDL-Colesterol/sangueRESUMO
Objective: The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients. Methods: Patients with HIV infection combined with anemia admitted to the Kunming Third People's Hospital were retrospectively collected and divided into mild anemia, moderate anemia, and severe anemia groups by peripheral hemoglobin (HB) content and calculated the ratio of ventricular septum density (VSD) to left ventricular density (LVD) and VSD to right ventricular density (RVD); then, the above patients were divided into the critical value group and the non-critical value group according to HB and compared the differences of LVD, RVD, VSD/LVD, and VSD/RVD in the two groups of patients. Results: A total of 126 patients were included, with a mean age of 47.9 ± 11.1 years; 43 cases were in the mild anemia group, 59 cases were in the moderate anemia group, and 24 cases were in the severe anemia group; the differences in LVD, RVD, VSD/LVD, and VSD/RVD were significant in the three groups; VSD/LVD was an independent predictor for the diagnosis of anemia critical value in the non-critical value group vs critical value group by multifactorial binary logistic regression analysis, and the ROC was plotted using VSD/LVD with an area under the curve of 0.731. Conclusions: The measurement of cardiac cavity density and ventricular septal density under CT plain film scan has a high accuracy in evaluating the severity of anemia in patients with HIV infection and can quickly determine the severity of HIV infection in the early stage and treat it as soon as possible.
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BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.
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5'-Nucleotidase , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/imunologia , Animais , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/metabolismo , Camundongos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Progressão da DoençaRESUMO
Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk.
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Pressão Sanguínea , Doenças Cardiovasculares , População do Leste Asiático , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , População do Leste Asiático/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hipertensão/genética , Hipertensão/epidemiologia , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.
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Cardiolipinas , Corantes Fluorescentes , Lipossomas Unilamelares , Cardiolipinas/química , Corantes Fluorescentes/química , Lipossomas Unilamelares/química , Propriedades de Superfície , Lipossomos/química , Cloreto de Sódio/química , Tensoativos/química , Estrutura MolecularRESUMO
BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.
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Senescência Celular , Células Epiteliais , Exossomos , Túbulos Renais , Macrófagos , MicroRNAs , Telômero , MicroRNAs/genética , MicroRNAs/metabolismo , Senescência Celular/genética , Exossomos/metabolismo , Exossomos/genética , Animais , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Macrófagos/metabolismo , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Camundongos , Telômero/genética , Telômero/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Masculino , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Fibrose/genética , Angiotensina IIRESUMO
Fluorescence is an essential property of molecules and materials that plays a pivotal role across various areas such as lighting, sensing, imaging, and other applications. For instance, temperature-sensitive fluorescence emission is widely utilized for chemo-/biosensing but usually decreases the intensity upon the increase in temperature. In this study, we observed a temperature-induced enhancement of up to â¼150 times in two-photon fluorescence (TPF) emission from a dye molecule, 4-(4-diethylaminostyry)-1-methylpyridinium iodide (D289), as it interacted with binary complex vesicles composed of two commonly applied surfactants: sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB). By employing second harmonic generation (SHG) and TPF techniques, we clearly revealed the temperature-dependent kinetic behavior of D289 on the surface of the vesicles and utilized it to interpret the origin of the significant TPF enhancement. Additionally, we also demonstrated a similar heating-induced enhancement of the TPF emission from D289 on the membrane of phospholipid vesicles, indicating the potential application of TPF in temperature sensing in the biology systems. The embedding of D289 in the tightly packed alkane chains was identified as the key factor in enhancing the TPF emission from D289. This finding may provide valuable information for synthesizing fluorescence materials with a high optical yield.
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OBJECTIVE: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children. METHODS: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models. RESULTS: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant. CONCLUSION: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children.
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Eosinófilos , Paragonimíase , Tomografia Computadorizada por Raios X , Tuberculose Pleural , Humanos , Paragonimíase/diagnóstico , Paragonimíase/diagnóstico por imagem , Masculino , Feminino , Criança , Estudos Retrospectivos , Diagnóstico Diferencial , Tuberculose Pleural/diagnóstico , Pré-Escolar , Adolescente , Curva ROC , Sensibilidade e EspecificidadeRESUMO
ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.
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Adenosina Desaminase , Receptores ErbB , Hepatócitos , Helicase IFIH1 Induzida por Interferon , Fígado , Macrófagos , Camundongos Knockout , Progranulinas , Animais , Adenosina Desaminase/metabolismo , Adenosina Desaminase/genética , Receptores ErbB/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Progranulinas/metabolismo , Progranulinas/genética , Fígado/metabolismo , Fígado/imunologia , Fígado/patologia , Hepatócitos/metabolismo , Camundongos , Helicase IFIH1 Induzida por Interferon/metabolismo , Helicase IFIH1 Induzida por Interferon/genética , Transdução de Sinais , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos Endogâmicos C57BL , RNA de Cadeia Dupla/metabolismo , Edição de RNARESUMO
PURPOSE: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC. METHODS: 873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software. RESULTS: The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE. CONCLUSION: This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
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5'-Nucleotidase , Biomarcadores Tumorais , Carcinoma Hepatocelular , Quimiocina CCL17 , Proteínas Ligadas por GPI , Neoplasias Hepáticas , Receptores CCR4 , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/imunologia , Quimiocina CCL17/metabolismo , Feminino , Masculino , Prognóstico , Receptores CCR4/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , 5'-Nucleotidase/metabolismo , Estudos Retrospectivos , Microambiente Tumoral/imunologia , Proteínas Ligadas por GPI/metabolismo , Idoso , AdultoRESUMO
Designing high-performance polarization-sensitive photodetectors is essential for photonic device applications. Anisotropic one-dimensional (1D) van der Waals (vdW) materials have provided a promising platform to that end. Despite significant advances in 1D vdW photonic devices, their performance is still far from delivering practical potential. Herein, we propose the design of high-performance polarization-sensitive photodetectors using unique 1D vdW materials. By leveraging the chemical vapor transport technique, we successfully fabricate high-quality 1D vdW Nb2Pd1-xSe5 (x = 0.29) nanowires. The 1D vdW Nb2Pd1-xSe5 photodetector exhibits a high mobility of â¼56 cm2/(V s) and superior photoresponse performance, including a high responsivity of 1A/W and an ultrafast response time of â¼8 µs under 638 nm illumination. Moreover, the 1D vdW Nb2Pd1-xSe5 photodetector demonstrates excellent polarization-sensitive photoresponse with a degree of linear polarization (DOLP) up to 0.85 and can be modulated by adjusting the gate voltage, laser power density, and wavelength. Those exceptional performance are believed to be relevant to the symmetry-reduction induced by the partial occupation of Pd sites. This study offers feasible approaches to enhance the anisotropy of 1D vdW materials and the modulation of their polarization-sensitive photoresponse, which may provide deep insights into the physical origin of anisotropic properties of 1D vdW materials.
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Glycated hemoglobin (HbA1c), originating from the non-enzymatic glycosylation of ßVal1 residues in hemoglobin (Hb), is an essential biomarker indicating average blood glucose levels over a period of 2 to 3 months without external environmental disturbances, thereby serving as the gold standard in the management of diabetes instead of blood glucose testing. The emergence of HbA1c biosensors presents affordable, readily available options for glycemic monitoring, offering significant benefits to small-scale laboratories and clinics. Utilizing nanomaterials coupled with high-specificity probes as integral components for recognition, labeling, and signal transduction, these sensors demonstrate exceptional sensitivity and selectivity in HbA1c detection. This review mainly focuses on the emerging probes and strategies integral to HbA1c sensor development. We discussed the advantages and limitations of various probes in sensor construction as well as recent advances in diverse sensing strategies for HbA1c measurement and their potential clinical applications, highlighting the critical gaps in current technologies and future needs in this evolving field.
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Técnicas Biossensoriais , Hemoglobinas Glicadas , Hemoglobinas Glicadas/análise , Técnicas Biossensoriais/métodos , Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/sangue , Glicemia/análiseRESUMO
Uncrewed Aerial Spray Systems (UASS), commonly called drones, have become an important application technique for plant protection products in Asia and worldwide. As such, environmental variables and spray system parameters influencing spray drift deserve detailed investigations. This study presents the data analysis of 114 UASS drift trials conducted between December 2021 and December 2022 in China. Study design was based on the ISO 22866:2005 protocol for spray drift trials and considered different UASS platforms, nozzles, and release heights, and specifically continuously measured weather conditions. The relative importance of the environmental variables and spray system parameters was evaluated by a random forest (RF) feature importance analysis, a Sobol sensitivity analysis and partial dependence plots. This approach was preferred to linear ranking techniques such as ANOVA (analysis of variance) due to the non-linearity of the system. In addition, partial dependence plots are proposed to visualize the relationship between specific input parameters within the system. Drift deposition curves calculated from the 114 trials show good agreement with previous UASS trials reported in the literature. As reported in previous studies, spray drift following UASS applications is lower than for manned aerial vehicles, greater than for ground spray applications, and similar to drift observed from orchard air blast applications. In addition, 9 trials were conducted on corn fields in order to evaluate the potential effect of crop cover on spray drift. Spray drift was observed to be reduced over the cropped soil, suggesting that plant cover might possibly reduce spray drift. These findings could help supporting drift mitigation policies, stewardship advice and product labelling around the world.
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BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.
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Angiotensina II , Fibrose , Hipertensão , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Endogâmicos C57BL , Vimentina , Animais , Angiotensina II/toxicidade , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fibrose/induzido quimicamente , Camundongos , Humanos , Vimentina/metabolismo , Masculino , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/patologia , Camundongos Knockout , Proteínas com Domínio LIM/metabolismo , Proteínas com Domínio LIM/genéticaRESUMO
OBJECTIVES: Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this study is to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. METHODS: Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV, laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. RESULTS: Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6â¯%, 4.6 and 14.9â¯%, 8.3 and 25.7â¯%, and 10.0 and 34.4â¯% for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2â¯%, 2.5-14.7â¯%, 9.9-31.0â¯%, and 10.0-35.5â¯%, respectively. CONCLUSIONS: The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.
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PURPOSE: This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs). RESULTS: A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1-7.3), and the median OS was 15.3 months (95% CI: 12.9-17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients. CONCLUSION: The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Checkpoint Imunológico , Intervalo Livre de Progressão , Humanos , Idoso , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Resultado do Tratamento , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Taxa de SobrevidaRESUMO
BACKGROUND: To demonstrate the effectiveness and feasibility of robotic portal resection (RPR) for mediastinal tumour using a prospectively collected database. METHODS: Data from 73 consecutive patients with mediastinal tumours who underwent RPRs were prospectively collected from August 2018 to April 2023. All patients underwent chest and abdominal enhanced computed tomography (CT) and preoperative multidisciplinary team (MDT) discussion. The patients were stratified into two groups based on tumour size: Group A (tumour size < 4 cm) and Group B (tumour size ≥ 4 cm). General clinical characteristics, surgical procedures, and short outcomes were promptly recorded. RESULTS: All of the cases were scheduled for RPRs. One patient (1/73, 1.4%) was switched to a small utility incision approach because of extensive pleural adhesion. Two patients (2.8%) converted to sternotomy, however, no perioperative deaths occurred. Most of the tumours were located in the anterior mediastinum (51/73, 69.9%). Thymoma (27/73, 37.0%) and thymic cyst (16/73, 21.9%) were the most common diagnoses. The median diameter of tumours was 3.2 cm (IQR, 2.4-4.5 cm). The median total operative time was 61.0 min (IQR, 50.0-90.0 min). The median intraoperative blood loss was 20 mL (IQR, 5.0-30.0 ml), and only one patient (1.4%) experienced an intraoperative complication. The median length of hospital stay was 3 days (IQR, 2-4 days). Compared with Group A, the median total operative time and console time of Group B were significantly longer (P = 0.006 and P = 0.003, respectively). The volume of drainage on the first postoperative day was greater in group B than in group A (P = 0.013). CONCLUSION: RPR is a safe and effective technique for mediastinal tumour treatment, which can expand the application of minimally invasive surgery for the removal of complicated mediastinal tumours.
Assuntos
Neoplasias do Mediastino , Procedimentos Cirúrgicos Robóticos , Robótica , Timoma , Neoplasias do Timo , Humanos , Neoplasias do Mediastino/cirurgia , Robótica/métodos , Neoplasias do Timo/cirurgia , Timoma/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.